Central sleep apnea is a type of sleep-disordered breathing that is characterized by a failure of the sleeping brain to generate regular, rhythmic bursts of neural activity. The resulting cessation of rhythmic breathing, referred to as apnea, represents a disorder of the respiratory control system responsible for regulating the rate and depth of breathing, i.e. overall pulmonary ventilation. Central sleep apnea should be contrasted with obstructive sleep apnea, where the proximate cause of apnea is obstruction of the pharyngeal airway despite ongoing rhythmic neural outflow to the respiratory muscles. The difference between central sleep apnea and obstructive sleep apnea is clearly established, and the two can co-exist. While central sleep apnea can occur in a number of clinical settings, it is most commonly observed in association with heart failure or cerebral vascular insufficiency. An example of central sleep apnea is Cheyne-Stokes respiration.
The respiratory control system comprises a negative feedback system wherein a central pattern generator creates rhythmic bursts of activity when respiratory chemo-receptors sensing carbon dioxide, oxygen and pH are adequately stimulated (FIG. 1). While this neural output of the brainstem central pattern generator to the respiratory muscles derives from a neural rhythm generated intrinsically by the central pattern generator, the generator becomes silent if the feedback signals, related to arterial PCO2 and PO2, are not sufficiently intense. In other words, the respiratory rhythm is generated by a conditional central pattern generator which requires an adequate input stimulus derived from peripheral chemoreceptors sensing arterial PCO2 and PO2 from central chemoreceptors sensing brain PCO2/pH. Furthermore, the intensity of neural activity generated by the respiratory central pattern generator depends directly upon the arterial PCO2 inversely on the arterial PO2. Thus, the central and peripheral chemoreflex loops constitute a negative feedback system regulating the arterial PO2 and PCO2, holding them constant within narrow limits (FIG. 1).
This normal regulation of arterial blood gases is accomplished by a stable ventilatory output of the respiratory central pattern generator. By contrast, central sleep apnea represents an instability of the respiratory control system. The instability can arise from one of two mechanisms, namely: (1) intrinsic failure of the respiratory central pattern generator in the face of adequate stimulation by respiratory chemoreceptors; or (2) lack of adequate stimulation of the central pattern generator by respiratory chemoreceptors. The former is referred to as the “intrinsic instability” and the latter is referred to as the “chemoreflex instability.” Theoretically, both mechanisms can co-exist. The common form of central sleep apnea is thought to be caused by the chemoreflex instability mechanism.
The chemoreflex control of breathing might exhibit instability either because the delay of the negative feedback signal is excessively long or because the gain of the system is excessively high. Current evidence indicates that the latter constitutes the principal derangement in central sleep apnea caused by heart failure. Specifically, the overall response of the control system to a change in arterial PCO2 is three-fold higher in heart-failure patients with central sleep apnea than in those having no sleep-disordered breathing. This increased gain probably resides within the central chemoreflex loop; however, high gain of the peripheral chemoreflex loop cannot be excluded. Accordingly, the fundamental mechanism of central sleep apnea is taken to be high loop gain of the control system, which results in feedback instability during sleep.
Central sleep apnea causes repeated arousals and oxyhemoglobin desaturations. Although firm evidence linking central sleep apnea to morbidity and mortality is lacking, a variety of evidence leads to the inference that central sleep apnea may promote cardiac arhythmias, strokes, or myocardial infarctions. The repeated nocturnal arousals are likely to impair daytime cognitive function and quality of life. No treatment has become established as being effective for central sleep apnea. Stimulating drugs such as theophyline may be helpful, and carbonic anhydrase inhibitors may relieve central sleep apnea in normals sleeping at high altitude. Nasal continuous positive airway pressure may directly or indirectly improve ventilatory stability. Increasing inspired fractional concentration (F) of oxygen in the inspired gas generally does not eliminate central sleep apnea, whereas increasing inspired FCO2 (F|CO2=0.01–0.03) promptly eliminates central sleep apnea. However, long-term exposure to high F|CO2 would appear to be an undesirable long-term therapy.